scholarly journals Electroacupuncture Improved Hippocampal Neurogenesis following Traumatic Brain Injury in Mice through Inhibition of TLR4 Signaling Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Yuqin Ye ◽  
Yongxiang Yang ◽  
Chen Chen ◽  
Ze Li ◽  
Yanfeng Jia ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Signaling Pathway ◽  
Neurological Diseases ◽  
Inhibitory Effect ◽  
Protective Role ◽  
Hippocampal Neurogenesis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tlr4 Signaling ◽  
Tlr4 Signaling Pathway

The protective role of electroacupuncture (EA) treatment in diverse neurological diseases such as ischemic stroke is well acknowledged. However, whether and how EA act on hippocampal neurogenesis following traumatic brain injury (TBI) remains poorly understood. This study aims to investigate the effect of EA on hippocampal neurogenesis and neurological functions, as well as its underlying association with toll-like receptor 4 (TLR4) signaling in TBI mice. BrdU/NeuN immunofluorescence was performed to label newborn neurons in the hippocampus after EA treatment. Water maze test and neurological severity score were used to evaluate neurological function posttrauma. The hippocampal level of TLR4 and downstream molecules and inflammatory cytokines were, respectively, detected by Western blot and enzyme-linked immunosorbent assay. EA enhanced hippocampal neurogenesis and inhibited TLR4 expression at 21, 28, and 35 days after TBI, but the beneficial effects of EA on posttraumatic neurogenesis and neurological functions were attenuated by lipopolysaccharide-induced TLR4 activation. In addition, EA exerted an inhibitory effect on both TLR4/Myd88/NF-κB and TLR4/TRIF/NF-κB pathways, as well as the inflammatory cytokine expression in the hippocampus following TBI. In conclusion, EA promoted hippocampal neurogenesis and neurological recovery through inhibition of TLR4 signaling pathway posttrauma, which may be a potential approach to improve the outcome of TBI.

scholarly journals The Absence of TLR4 Prevents Fetal Brain Injury in the Setting of Intrauterine Inflammation

2018 ◽  
Vol 26 (8) ◽  
pp. 1082-1093 ◽  
Author(s):  
Natalia M. Tulina ◽  
Amy G. Brown ◽  
Guillermo O. Barila ◽  
Michal A. Elovitz
Keyword(s):  
Brain Injury ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Quantitative Polymerase Chain Reaction ◽  
Fetal Brain ◽  
Notch Signaling Pathway ◽  
Mouse Strains ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tlr4 Signaling ◽  
Tlr4 Signaling Pathway

Background: Exposure to intrauterine inflammation during pregnancy is linked to brain injury and neurobehavioral disorders in affected children. Innate immunity, specifically Toll-like receptor (TLR) signaling pathways are present throughout the reproductive tract as well as in the placenta, fetal membranes, and fetus. The TLR pathways are mechanistically involved in host responses to foreign pathogens and may lead to brain injury associated with prenatal inflammation. Objective: We aimed to determine whether the activation of the TLR4 signaling pathway, in the mother and fetus, is critical to fetal brain injury in the setting of intrauterine inflammation. Methods: A mini-laparotomy was performed on time pregnant C57B6 mice and 2 knockout mouse strains lacking the function of the Tlr4 and Myd88 genes on embryonic day 15. Intrauterine injections of Escherichia coli lipopolysaccharide or saline were administered as described previously. Dams were killed 6 hours postsurgery, and placental, amniotic fluid, and fetal brain tissue were collected. To assess brain injury, quantitative polymerase chain reaction (qPCR) analysis was performed on multiple components of the NOTCH signaling pathway, including Hes genes. Interleukin (IL) IL6, IL1β, and CCL5 expression was assessed using qPCR and enzyme-linked immunosorbent assay. Results: Using an established mouse model of intrauterine inflammation, we demonstrate that the abrogation of TLR4 signaling eliminates the cytokine response in mother and fetus and prevents brain injury associated with increased expression of transcriptional effectors of the NOTCH signaling pathway, Hes1 and Hes5. Conclusions: These data show that the activation of the TLR4 signaling pathway is necessary for the development of fetal brain injury in response to intrauterine inflammation.

scholarly journals Activation of Sphingosine 1-Phosphate Receptor 1 Enhances Hippocampus Neurogenesis in a Rat Model of Traumatic Brain Injury: An Involvement of MEK/Erk Signaling Pathway

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Yuqin Ye ◽  
Zhenyu Zhao ◽  
Hongyu Xu ◽  
Xin Zhang ◽  
Xinhong Su ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Signaling Pathway ◽  
Hippocampal Neurogenesis ◽  
Mitogen Activated Protein Kinase ◽  
Erk Signaling ◽  
Future Research ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Sphingosine 1 Phosphate

Among sphingosine 1-phosphate receptors (S1PRs) family, S1PR1 has been shown to be the most highly expressed subtype in neural stem cells (NSCs) and plays a crucial role in the migratory property of NSCs. Recent studies suggested that S1PR1 was expressed abundantly in the hippocampus, a specific neurogenic region in rodent brain for endogenous neurogenesis throughout life. However, the potential association between S1PR1 and neurogenesis in hippocampus following traumatic brain injury (TBI) remains unknown. In this study, the changes of hippocampal S1PR1 expression after TBI and their effects on neurogenesis and neurocognitive function were investigated, focusing on particularly the extracellular signal-regulated kinase (Erk) signaling pathway which had been found to regulate multiple properties of NSCs. The results showed that a marked upregulation of S1PR1 occurred with a peak at 7 days after trauma, revealing an enhancement of proliferation and neuronal differentiation of NSCs in hippocampus due to S1PR1 activation. More importantly, it was suggested that mitogen-activated protein kinase-Erk kinase (MEK)/Erk cascade was required for S1PR1-meidated neurogenesis and neurocognitive recovery following TBI. This study lays a preliminary foundation for future research on promoting hippocampal neurogenesis and improving TBI outcome.

scholarly journals SHED-Derived Exosomes Regulate Microglial Polarization in the Treatment of Traumatic Brain Injury in Rats via miR-330-5p

2020 ◽  
Author(s):  
Ye Li ◽  
Xinxin Wang ◽  
Xiaoyu Cao ◽  
Na Li ◽  
Sun Meng ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Structural Damage ◽  
Inhibitory Effect ◽  
Deciduous Teeth ◽  
Luciferase Reporter ◽  
Enzyme Linked Immunosorbent Assay ◽  
M2 Polarization ◽  
M1 Polarization

Abstract Background: Traumatic brain injury (TBI) causes structural damage and impairs motor and cognitive function of the brain. Our previous study suggested that exosomes (EXs) secreted by stem cells from human exfoliated deciduous teeth (SHED) extenuated motor damage in TBI rats by regulating microglia. The molecular mechanism of SHED-EXs was investigated in the present study. Methods: The miRNA array was performed to determine the differential miRNA expression in SHED-EXs treating microglia. The key miRNA was selected. Flow cytometry, immunofluorescence, enzyme linked immunosorbent assay (ELISA) and Griess assay were performed to detect the function of key miRNA. Real-time PCR, Western blotting and dual luciferase reporter assay were used to confirm the relationship between key miRNA and the target gene. Chromatin immunoprecipitation (ChIP) was performed to determine the downstream pathway of EXs-miRNA. Traumatic brain injury rat model was established and local injection of EXs-miRNA was performed to evaluate the effect.Results: SHED-EXs delivery of miR-330-5p was the key in the regulation of microglia polarization by inhibiting M1 polarization and promoting M2 polarization. Mechanistically, miR-330-5p had an inhibitory effect on Ehmt2, and miR-330-5p/Ehmt2 promoted the transcription of CXCL14 through H3K9me2. In vivo data showed that SHED-EXs/miR-330-5p reduced neuro-inflammation and repaired neurological function of TBI rats. Conclusions: SHED-EXs/miR-330-5p improved the motor function of rats after TBI by inhibiting M1 polarization and promoting M2 polarization of microglia through Ehmt2/H3K9me2/CXCL14 pathway.

scholarly journals Glycyrrhizin Ameliorates Radiation Enteritis in Mice Accompanied by the Regulation of the HMGB1/TLR4 Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Xiao-min Zhang ◽  
Xiao Hu ◽  
Jin-ying Ou ◽  
Shan-shan Chen ◽  
Ling-hui Nie ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Radiation Enteritis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Intestinal Damage ◽  
Tlr4 Signaling ◽  
Pelvic Malignancies ◽  
Tlr4 Signaling Pathway ◽  
Anti Inflammatory

Radiation enteritis is a common side effect of radiotherapy for abdominal and pelvic malignancies, which can lead to a decrease in patients’ tolerance to radiotherapy and the quality of life. It has been demonstrated that glycyrrhizin (GL) possesses significant anti-inflammatory activity. However, little is known about its anti-inflammatory effect in radiation enteritis. In the present study, we aimed to investigate the potential anti-inflammatory effects of GL on radiation enteritis and elucidate the possible underlying molecular mechanisms involved. The C57BL/6 mice were subjected to 6.5 Gy abdominal X-ray irradiation to establish a model of radiation enteritis. Hematoxylin and eosin staining was performed to analyze the pathological changes in the jejunum. The expression of TNF-α in the jejunum was analyzed by immunochemistry. The levels of inflammatory cytokines, such as TNF-α, IL-6, IL-1β, and HMGB1 in the serum were determined by enzyme-linked immunosorbent assay. The intestinal absorption capacity was tested using the D-xylose absorption assay. The levels of HMGB1 and TLR4 were analyzed by western blotting and immunofluorescence staining. We found that GL significantly alleviated the intestinal damage and reduced the levels of inflammatory cytokines, such as TNF-α, IL-6, IL-1β, and HMGB1 levels. Furthermore, the HMGB1/TLR4 signaling pathway was significantly downregulated by GL treatment. In conclusion, these findings indicate that GL has a protective effect against radiation enteritis through the inhibition of the intestinal damage and the inflammatory responses, as well as the HMGB1/TLR4 signaling pathway. Thereby, GL might be a potential therapeutic agent for the treatment of radiation enteritis.

Manual acupuncture relieves microglia-mediated neuroinflammation in a rat model of traumatic brain injury by inhibiting the RhoA/ROCK2 pathway

2020 ◽  
Vol 38 (6) ◽  
pp. 426-434
Author(s):  
Ming-min Zhu ◽  
Ji-huan Lin ◽  
Peng Qing ◽  
Liu Pu ◽  
Shu-lian Chen ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Signaling Pathway ◽  
Inflammatory Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Manual Acupuncture ◽  
Sprague Dawley ◽  
Tissue Samples ◽  
M1 Polarization ◽  
Immunofluorescence Labeling

Objective: To investigate the regulatory mechanism of manual acupuncture (MA) on microglial polarization–mediated neuroinflammation after traumatic brain injury (TBI), focusing on the RhoA/Rho-associated coiled coil-forming protein kinase (ROCK2) pathway. Methods: Sprague Dawley (SD) rats were used to generate a TBI model using Feeney’s freefall epidural impact method. MA was performed on half of the TBI model rats, while the others remained untreated. Acupuncture was administered at GV15, GV16, GV20, GV26, and LI4. At the end of the intervention, rat brain tissue samples were collected, and the microglial M1 polarization status was observed by immunofluorescence labeling of CD86, an M1 microglia-specific protein. RhoA/ROCK2 signaling components were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. An enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of inflammatory factors. Results: Compared with normal rats, the CD86 expression density in the untreated TBI model rats was high and showed an aggregated expression pattern. The genes and proteins of the RhoA/ROCK2 signaling pathway were highly expressed, and inflammatory factors were significantly increased. The CD86 expression density in TBI rats after MA was reduced compared to that in untreated TBI rats and showed a scattered distribution. The expression of RhoA/ROCK2 signaling pathway genes and proteins was also significantly reduced, and inflammatory factors were decreased. Conclusion: These results show that MA may inhibit M1 polarization of microglia by regulating the RhoA/ROCK2 signaling pathway, thereby reducing neuroinflammation in TBI.

Hyperoxia-induced immature brain injury through the TLR4 signaling pathway in newborn mice

2015 ◽  
Vol 1610 ◽  
pp. 51-60 ◽  
Author(s):  
Yang Liu ◽  
Pu Jiang ◽  
Min Du ◽  
Kun Chen ◽  
Amber Chen ◽  
...  
Keyword(s):  
Brain Injury ◽  
Signaling Pathway ◽  
Immature Brain ◽  
Tlr4 Signaling ◽  
Newborn Mice ◽  
Tlr4 Signaling Pathway
Sign in / Sign up

Export Citation Format

Share Document